The present invention relates to n-butyric acid derivatives and their use as a drug.
It is known that the n-butyric acid salts, and most particularly sodium butyrate, possess interesting inhibiting actions on the growth of fibroblasts following actions on the histones and on the structure of the cellular nuclei chromatin. This inhibiting action of the cellular division has proved particularly important to explore in oncology, notably for the treatment of various leukemias, or various sarcomas or carcinomas. In addition to these antimitotic actions at the level of the cellular nuclei, antiviral actions of sodium butyrate have also been characterized for the herpes virus. However, it is also known following pharmacokinetic tests that the mineral salts of n-butyric acid have a lifetime in vivo which is extremely short. In attempts for increasing the half-life of the injected product, other derivatives have also been proposed, as for example the arginine butyrate (Ch. CHANY et al, Int. J. Cancer, 1982, 30, 489; ibid. 1983, 32, 379 and Patent Application EP-A1-0 069 659 (INSERM)). These ionic derivatives do not provide a sufficient in vivo half lifetime for a satisfactory pharmacologic action since they are very quickly eliminated after administration by the intravenous route.
Thus, if sodium n-butyrate is injected at time t=0 by the i.v. route and at the rate of 0.12 g per kilogramme of rabbit, the dosages of the n-butyric acid present in mmol per liter of serum are at time t=2 min: 1.66 mmol/l; 5 min: 0.87 mmol/l; 18 min: 0.03 mmol/l; 30 min: 0.02 mmol/l.
Under the same conditions, arginine n-butyrate gives the following results: 2 min: 1.36 mmol/l; 5 min: 0.23 mmol/l; 30 min: 0.06 mmol/l; 60 min: 0 mmol/l.
These pharmacokinetic results show that the half life of these compounds in the rabbit blood stream is very short and less than 5 min.
Starting from conclusions admitted at present from the studies made, it is admitted that, for the hereabove saline n-butyrates, the product which is biologically active is the n-butyric acid.